Thallium reinjection protocols have the disadvantage of requiring 3 sets of images, after exercise, 3-4 hr redistribution, and reinjection. An attractive alternative is to reinject 1 mCi of thallium immediately after the exercise images and imaging 3-4 hrs later, yielding a modified redistribution (mRD) image representing redistribution of both the initial and the reinjected thallium doses. To determine the adequacy of exercise and MRD images in identifying reversible defects, we studied 23 patients with chronic coronary artery disease by exercise thallium SPECT. In addition to exercise and MRD images, we also reinjected another 1 Mci of thallium after the MRD image at 3-4 hrs. The exercise, MRD, and 3-4 hr reinjection images were then normalized and analyzed quantitatively. Of the 50 abnormal regions on the exercise images, 23 (46%) were irreversible on MRD. However, 6 (26%) of these irreversible defects (involving 5 of the 23 patients) reversed after 3-4 hr reinjection, with mean thallium activities increasing from 57+/-5 (exercise) and 63+/-4 (MRD) to 74+/-7 (p<0.001). Only 1 of 27 reversible regions on MRD appeared irreversible after 3-4 hr reinjection. All regions with reversibility only on 3-4 hr reinjection images were supplied by critically stenosed coronary arteries. These data suggest MRD imaging will overestimate myocardial fibrosis in roughly 1/4 of irreversible defects and that a 3-4 hr delay is necessary for accurate determination of myocardial ischemia and viability.